Inflammatory Breast Cancer: Clinical Implications of Genomic Alterations and Mutational Profiling

Abstract

Inflammatory breast cancer (IBC) is a rare and aggressive type of breast cancer whose molecular basis is poorly understood. We performed a comprehensive molecular analysis of 24 IBC biopsies naïve of treatment, using a high-resolution microarray platform and targeted next-generation sequencing (105 cancer-related genes). The genes more frequently affected by gains were MYC (75%) and MDM4 (71%), while frequent losses encompassed TP53 (71%) and RB1 (58%). Increased MYC and MDM4 protein expression levels were detected in 18 cases. These genes have been related to IBC aggressiveness, and MDM4 is a potential therapeutic target in IBC. Functional enrichment analysis revealed genes associated with inflammatory regulation and immune response. High homologous recombination (HR) deficiency scores were detected in triple-negative and metastatic IBC cases. A high telomeric allelic imbalance score was found in patients having worse overall survival (OS). The mutational profiling was compared with non-IBC (TCGA, n = 250) and IBC (n = 118) from four datasets, validating our findings. Higher frequency of TP53 and BRCA2 variants were detected compared to non-IBC, while PIKC3A showed similar frequency. Variants in mismatch repair and HR genes were associated with worse OS. Our study provided a framework for improved diagnosis and therapeutic alternatives for this aggressive tumor type.

Transcriptomic intratumor heterogeneity of breast cancer patient-derived organoids may reflect the unique biological features of the tumor of origin

“…We further investigated PDO155 which was derived from a patient with IBC. The patient developed liver metastases early after surgery and had a poor clinical outcome [ 22 , 23 ]. To our knowledge, no reports are available on PDO lines being established from patients with IBC and then precisely analyzed.…”

Small extracellular vesicle-encapsulated miR-181b-5p, miR-222-3p and let-7a-5p: Next generation plasma biopsy-based diagnostic biomarkers for inflammatory breast cancer

“…Inflammatory breast cancer (IBC) is the most lethal locally advanced breast cancer variant [ 1 ]. It is a relatively infrequent aggressive form of cancer that grows within the dermal lymphatics of breast tissue.…”

“…The 5- year overall survival rate of IBC is 55% shorter than that of non-inflammatory breast cancer (non-IBC), with a median survival of 2.9 to 3.8 years[ 4 , 5 ]. Further, approximately 75% of IBC patients are pathologically diagnosed with lymph vascular tumor emboli, which accounts for strong metastatic behavior and poor prognosis [ 1 ]. IBC diagnosis is challenged by overlapping signs and symptoms of other diseases, and approximately 30% of newly diagnosed cases with distant metastases [ 6 ].…”

SCAMP3 Regulates EGFR and Promotes Proliferation and Migration of Triple-Negative Breast Cancer Cells through the Modulation of AKT, ERK, and STAT3 Signaling Pathways

“…IBC is a rare, aggressive, and deadliest type of breast cancer characterized by its mechanism of invasion and metastasis. The lethality of IBC is due to its ability to invade the vascular and lymphatic systems through the generation of emboli and the development of subsequent metastases [ 46 ]. We published an increase in SCAMP3 expression in the hallmark emboli structure and in lymphatic vessels of IBC tumor samples [ 10 ].…”